{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:19:45Z","timestamp":1787959185618,"version":"build-2784847793"},"reference-count":76,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T00:00:00Z","timestamp":1671408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxic ischemic (HI) brain injury that occurs during neonatal period has been correlated with severe neuronal damage, behavioral deficits and infant mortality. Previous evidence indicates that N-acetylcysteine (NAC), a compound with antioxidant action, exerts a potential neuroprotective effect in various neurological disorders including injury induced by brain ischemia. The aim of the present study was to investigate the role of NAC as a potential therapeutic agent in a rat model of neonatal HI brain injury and explore its long-term behavioral effects. To this end, NAC (50 mg\/kg\/dose, i.p.) was administered prior to and instantly after HI, in order to evaluate hippocampal and cerebral cortex damage as well as long-term functional outcome. Immunohistochemistry was used to detect inducible nitric oxide synthase (iNOS) expression. The results revealed that NAC significantly alleviated sensorimotor deficits and this effect was maintained up to adulthood. These improvements in functional outcome were associated with a significant decrease in the severity of brain damage. Moreover, NAC decreased the short-term expression of iNOS, a finding implying that iNOS activity may be suppressed and that through this action NAC may exert its therapeutic action against neonatal HI brain injury.<\/jats:p>","DOI":"10.3390\/ijms232416175","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T05:25:46Z","timestamp":1671427546000},"page":"16175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["N-Acetylcysteine Administration Attenuates Sensorimotor Impairments Following Neonatal Hypoxic-Ischemic Brain Injury in Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"Evangelia","family":"Kesidou","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Neurology and Neuroimmunology, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 546 36 Thessaloniki, Greece"},{"name":"Laboratory of Physiology, Faculty of Medicine, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Bitsina","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurology and Neuroimmunology, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 546 36 Thessaloniki, Greece"},{"name":"Laboratory of Physiology, Faculty of Medicine, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5415-2064","authenticated-orcid":false,"given":"Athanasios","family":"Chatzisotiriou","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Faculty of Medicine, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8607-6695","authenticated-orcid":false,"given":"Paschalis","family":"Theotokis","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurology and Neuroimmunology, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 546 36 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia","family":"Dandi","sequence":"additional","affiliation":[{"name":"Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5563-4017","authenticated-orcid":false,"given":"Despina A.","family":"Tata","sequence":"additional","affiliation":[{"name":"Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Spandou","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Faculty of Medicine, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0140-6736(05)71048-5","article-title":"4 million neonatal deaths: When? Where? Why?","volume":"365","author":"Lawn","year":"2005","journal-title":"Lancet (Lond. Engl.)"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fncel.2017.00078","article-title":"Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges","volume":"11","author":"Millar","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1001\/archpediatrics.2011.1772","article-title":"Hypothermia for neonatal hypoxic ischemic encephalopathy: An updated systematic review and meta-analysis","volume":"166","author":"Tagin","year":"2012","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/S0095-5108(18)30050-2","article-title":"Long-term neurodevelopmental outcome of asphyxiated newborns","volume":"26","author":"Simon","year":"1999","journal-title":"Clin. Perinatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1056\/NEJMra041996","article-title":"Neonatal brain injury","volume":"351","author":"Ferriero","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1053\/j.semperi.2004.10.003","article-title":"Brain injury in the term infant","volume":"28","author":"Perlman","year":"2004","journal-title":"Semin. Perinatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.clp.2018.01.015","article-title":"Perinatal Brain Injury: Mechanisms, Prevention, and Outcomes","volume":"45","author":"Novak","year":"2018","journal-title":"Clin. Perinatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0095-5108(02)00059-3","article-title":"Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: Current concepts","volume":"29","author":"Grow","year":"2002","journal-title":"Clin. Perinatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1742-2094-6-13","article-title":"Neuroinflammation and MMPs: Potential therapeutic targets in neonatal hypoxic-ischemic injury","volume":"6","author":"Leonardo","year":"2009","journal-title":"J. Neuroinflamm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1203\/00006450-199604000-00004","article-title":"Cerebral metabolism within 18 hours of birth asphyxia: A proton magnetic resonance spectroscopy study","volume":"39","author":"Hanrahan","year":"1996","journal-title":"Pediatr. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101256","DOI":"10.1016\/j.siny.2021.101256","article-title":"Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury","volume":"26","author":"Chakkarapani","year":"2021","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Roumes, H., Goudeneche, P., Pellerin, L., and Bouzier-Sore, A.K. (2022). Resveratrol and Some of Its Derivatives as Promising Prophylactic Treatments for Neonatal Hypoxia-Ischemia. Nutrients, 14.","DOI":"10.3390\/nu14183793"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Perrone, S., Lembo, C., Gironi, F., Petrolini, C., Catalucci, T., Corbo, G., Buonocore, G., Gitto, E., and Esposito, S.M.R. (2022). Erythropoietin as a Neuroprotective Drug for Newborn Infants: Ten Years after the First Use. Antioxidants, 11.","DOI":"10.3390\/antiox11040652"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/jama.2017.7218","article-title":"Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial","volume":"318","author":"Shankaran","year":"2017","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101257","DOI":"10.1016\/j.siny.2021.101257","article-title":"Unanswered questions regarding therapeutic hypothermia for neonates with neonatal encephalopathy","volume":"26","author":"Sabir","year":"2021","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Park, W.S., Sung, S.I., Ahn, S.Y., Yoo, H.S., Sung, D.K., Im, G.H., Choi, S.J., and Chang, Y.S. (2015). Hypothermia augments neuroprotective activity of mesenchymal stem cells for neonatal hypoxic-ischemic encephalopathy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120893"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.parkreldis.2015.02.020","article-title":"Cerebrospinal fluid concentrations of N-acetylcysteine after oral administration in Parkinson\u2019s disease","volume":"21","author":"Katz","year":"2015","journal-title":"Park. Relat. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1046\/j.1471-4159.2003.01580.x","article-title":"The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice","volume":"84","author":"Farr","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s00134-007-0880-z","article-title":"Postresuscitation N-acetylcysteine treatment reduces cerebral hydrogen peroxide in the hypoxic piglet brain","volume":"34","author":"Lee","year":"2008","journal-title":"Intensive Care Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/sj.bjp.0703421","article-title":"Beneficial effects of n-acetylcysteine on ischaemic brain injury","volume":"130","author":"Cuzzocrea","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/brb3.208","article-title":"N-acetylcysteine (NAC) in neurological disorders: Mechanisms of action and therapeutic opportunities","volume":"4","author":"Harrigan","year":"2014","journal-title":"Brain Behav."},{"key":"ref_22","first-page":"1","article-title":"Cellular thiols and reactive oxygen species in drug-induced apoptosis","volume":"296","author":"Davis","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s000180300001","article-title":"Molecular mechanisms of N-acetylcysteine actions","volume":"60","author":"Zafarullah","year":"2003","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gutziet, O., Iluz, R., Ben Asher, H., Segal, L., Ben Zvi, D., Ginsberg, Y., Khatib, N., Zmora, O., Ross, M.G., and Weiner, Z. (2021). Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413629"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0891-5849(97)00137-8","article-title":"N-acetyl cysteine inhibits induction of no production by endotoxin or cytokine stimulated rat peritoneal macrophages, C6 glial cells and astrocytes","volume":"24","author":"Pahan","year":"1998","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20354","DOI":"10.1074\/jbc.273.32.20354","article-title":"Cytokine-mediated induction of ceramide production is redox-sensitive. Implications to proinflammatory cytokine-mediated apoptosis in demyelinating diseases","volume":"273","author":"Singh","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0006-8993(03)02244-3","article-title":"N-Acetyl cysteine protects against injury in a rat model of focal cerebral ischemia","volume":"971","author":"Sekhon","year":"2003","journal-title":"Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.neures.2016.01.008","article-title":"Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia","volume":"108","author":"Nie","year":"2016","journal-title":"Neurosci. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1203\/01.pdr.0000215045.91122.44","article-title":"Combination of systemic hypothermia and N-acetylcysteine attenuates hypoxic-ischemic brain injury in neonatal rats","volume":"59","author":"Jatana","year":"2006","journal-title":"Pediatr. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.neuropharm.2017.06.004","article-title":"Vitamin D improves functional outcomes in neonatal hypoxic ischemic male rats treated with N-acetylcysteine and hypothermia","volume":"123","author":"Lowe","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1177\/0271678X18765828","article-title":"N-Acetylcysteine rapidly replenishes central nervous system glutathione measured via magnetic resonance spectroscopy in human neonates with hypoxic-ischemic encephalopathy","volume":"38","author":"Moss","year":"2018","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"764251","DOI":"10.1155\/2015\/764251","article-title":"Protective Effects of N-Acetyl-L-Cysteine in Human Oligodendrocyte Progenitor Cells and Restoration of Motor Function in Neonatal Rats with Hypoxic-Ischemic Encephalopathy","volume":"2015","author":"Park","year":"2015","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1089\/ars.2010.3581","article-title":"Neuronal death and oxidative stress in the developing brain","volume":"14","author":"Ikonomidou","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0892-0362(99)00069-0","article-title":"Age-related changes in reactive oxygen species production in rat brain homogenates","volume":"22","author":"Driver","year":"2000","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0165-3806(00)00112-7","article-title":"Alterations in glutathione and amino acid concentrations after hypoxia-ischemia in the immature rat brain","volume":"125","author":"Wallin","year":"2000","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhao, M., Zhu, P., Fujino, M., Zhuang, J., Guo, H., Sheikh, I., Zhao, L., and Li, X.K. (2016). Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122078"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1550-2783-2-2-38","article-title":"The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stress","volume":"2","author":"Kerksick","year":"2005","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000085978","article-title":"Perinatal hypoxic-ischemic brain damage: Evolution of an animal model","volume":"27","author":"Vannucci","year":"2005","journal-title":"Dev. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/BF00315011","article-title":"Temporal evolution of neuropathologic changes in an immature rat model of cerebral hypoxia: A light microscopic study","volume":"90","author":"Towfighi","year":"1995","journal-title":"Acta Neuropathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0006-8993(03)02436-3","article-title":"Neonatal cerebral hypoxia-ischemia causes lateralized memory impairments in the adult rat","volume":"973","author":"Arteni","year":"2003","journal-title":"Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0166-4328(95)00248-0","article-title":"Long-term effects of neonatal ischemic-hypoxic brain injury on sensorimotor and locomotor tasks in rats","volume":"78","author":"Jansen","year":"1996","journal-title":"Behav. Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.brainres.2011.09.044","article-title":"Resveratrol ameliorates hypoxia\/ischemia-induced behavioral deficits and brain injury in the neonatal rat brain","volume":"1425","author":"Karalis","year":"2011","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1203\/00006450-199711000-00021","article-title":"Sensorimotor function and neuropathology five to six weeks after hypoxia-ischemia in seven-day-old rats","volume":"42","author":"Bona","year":"1997","journal-title":"Pediatr. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1161\/hs0901.094287","article-title":"Simvastatin protects against long-lasting behavioral and morphological consequences of neonatal hypoxic\/ischemic brain injury","volume":"32","author":"Balduini","year":"2001","journal-title":"Stroke"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0166-4328(00)00287-4","article-title":"Selective and long-term learning impairment following neonatal hypoxic-ischemic brain insult in rats","volume":"118","author":"Ikeda","year":"2001","journal-title":"Behav. Brain Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/ana.21066","article-title":"N-acetylcysteine reduces lipopolysaccharide-sensitized hypoxic-ischemic brain injury","volume":"61","author":"Wang","year":"2007","journal-title":"Ann. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/jnr.20087","article-title":"Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke","volume":"76","author":"Khan","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"ref_48","first-page":"1442","article-title":"Glutathione-dependent reductive stress triggers mitochondrial oxidation and cytotoxicity","volume":"26","author":"Zhang","year":"2012","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Jenkins, D.D., Moss, H.G., Brown, T.R., Yazdani, M., Thayyil, S., Montaldo, P., Vento, M., Kuligowski, J., Wagner, C., and Hollis, B.W. (2021). NAC and Vitamin D Improve CNS and Plasma Oxidative Stress in Neonatal HIE and Are Associated with Favorable Long-Term Outcomes. Antioxidants, 10.","DOI":"10.3390\/antiox10091344"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"867531","DOI":"10.1155\/2012\/867531","article-title":"Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent models: Implications for sex-specific neuroprotection in clinical neonatal practice","volume":"2012","author":"Hill","year":"2012","journal-title":"Neurol. Res. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.expneurol.2014.01.003","article-title":"Sex differences in behavioral outcome following neonatal hypoxia ischemia: Insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury","volume":"254","author":"Smith","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/jnr.23828","article-title":"Sex-dependent consequences of neonatal brain hypoxia-ischemia in the rat","volume":"95","author":"Netto","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12974-015-0251-6","article-title":"Sexually dimorphic outcomes and inflammatory responses in hypoxic-ischemic encephalopathy","volume":"12","author":"Mirza","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3389\/fped.2019.00211","article-title":"Sex Differences in Brain Injury and Repair in Newborn Infants: Clinical Evidence and Biological Mechanisms","volume":"7","author":"Rosenkrantz","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_55","first-page":"G152","article-title":"Effects of hypoxia and ischemia on autoregulation in postnatal intestine","volume":"261","author":"Nowicki","year":"1991","journal-title":"Am. J. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1159\/000327244","article-title":"Neuronal nitric oxide synthase inhibition prevents cerebral palsy following hypoxia-ischemia in fetal rabbits: Comparison between JI-8 and 7-nitroindazole","volume":"33","author":"Yu","year":"2011","journal-title":"Dev. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1341-8076.2005.00266.x","article-title":"Expression of inducible nitric oxide synthase and cyclooxygenase-2 mRNA in brain damage induced by lipopolysaccharide and intermittent hypoxia-ischemia in neonatal rats","volume":"31","author":"Yang","year":"2005","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.neuroscience.2008.07.007","article-title":"NF-kappaB signaling in cerebral ischemia","volume":"158","author":"Ridder","year":"2009","journal-title":"Neuroscience"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainres.2012.02.055","article-title":"Induction of inducible nitric oxide synthase by isoflurane post-conditioning via hypoxia inducible factor-1\u03b1 during tolerance against ischemic neuronal injury","volume":"1451","author":"Xu","year":"2012","journal-title":"Brain Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/jcbfm.1995.47","article-title":"Inducible nitric oxide synthase gene expression in brain following cerebral ischemia","volume":"15","author":"Iadecola","year":"1995","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9157","DOI":"10.1523\/JNEUROSCI.17-23-09157.1997","article-title":"Delayed reduction of ischemic brain injury and neurological deficits in mice lacking the inducible nitric oxide synthase gene","volume":"17","author":"Iadecola","year":"1997","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1515\/revneuro-2014-0041","article-title":"Nitric oxide synthase in hypoxic or ischemic brain injury","volume":"26","author":"Liu","year":"2015","journal-title":"Rev. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fneur.2018.00258","article-title":"Nitric Oxide Synthase Inhibition as a Neuroprotective Strategy Following Hypoxic-Ischemic Encephalopathy: Evidence From Animal Studies","volume":"9","author":"Cox","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1006\/niox.2001.0356","article-title":"N-acetylcysteine inhibits in vivo nitric oxide production by inducible nitric oxide synthase","volume":"5","author":"Bergamini","year":"2001","journal-title":"Nitric Oxide Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/jnr.20261","article-title":"N-acetylcysteine prevents endotoxin-induced degeneration of oligodendrocyte progenitors and hypomyelination in developing rat brain","volume":"78","author":"Paintlia","year":"2004","journal-title":"J. Neurosci. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/ana.410090206","article-title":"The influence of immaturity on hypoxic-ischemic brain damage in the rat","volume":"9","author":"Rice","year":"1981","journal-title":"Ann. Neurol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1749-6632.1997.tb48634.x","article-title":"A model of perinatal hypoxic-ischemic brain damage","volume":"835","author":"Vannucci","year":"1997","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1161\/01.STR.19.2.245","article-title":"Regional cerebral blood flow during hypoxia-ischemia in immature rats","volume":"19","author":"Vannucci","year":"1988","journal-title":"Stroke"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jneumeth.2017.06.016","article-title":"Modification to the Rice-Vannucci perinatal hypoxic-ischaemic encephalopathy model in the P7 rat improves the reliability of cerebral infarct development after 48h","volume":"288","author":"Edwards","year":"2017","journal-title":"J. Neurosci. Methods"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1161\/01.STR.18.2.503","article-title":"Motor performance in rats exposed to severe forebrain ischemia: Effect of fasting and 1,3-butanediol","volume":"18","author":"Combs","year":"1987","journal-title":"Stroke"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.bbr.2004.06.019","article-title":"Neurological reflexes and early motor behavior in rats subjected to neonatal hypoxic-ischemic injury","volume":"157","author":"Lubics","year":"2005","journal-title":"Behav. Brain Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1161\/01.STR.17.3.472","article-title":"Rat middle cerebral artery occlusion: Evaluation of the model and development of a neurologic examination","volume":"17","author":"Bederson","year":"1986","journal-title":"Stroke"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1161\/01.STR.26.4.644","article-title":"Environment influences functional outcome of cerebral infarction in rats","volume":"26","author":"Ohlsson","year":"1995","journal-title":"Stroke"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.brainres.2005.03.013","article-title":"Erythropoietin prevents long-term sensorimotor deficits and brain injury following neonatal hypoxia-ischemia in rats","volume":"1045","author":"Spandou","year":"2005","journal-title":"Brain Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1203\/00006450-199508000-00019","article-title":"Effect of status epilepticus on hypoxic-ischemic brain damage in the immature rat","volume":"38","author":"Cataltepe","year":"1995","journal-title":"Pediatr. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1203\/00006450-200008000-00021","article-title":"Increased plasma beta-hydroxybutyrate, preserved cerebral energy metabolism, and amelioration of brain damage during neonatal hypoxia ischemia with dexamethasone pretreatment","volume":"48","author":"Dardzinski","year":"2000","journal-title":"Pediatr. 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